This proposal describes a 5-year training program for the development of an academic career in pediatric hematology/oncology based on a basic research program studying gene targeting. The principal investigator (PI) has completed a residency in pediatrics (board certified), a fellowship in pediatric hematology/oncology (board certified), and is completing a Howard Hughes Medical Institute Post-Doctoral Fellowship for Physicians. The Mentored Clinical Scientist Development Award is uniquely suited to promote the career development of the PI as he transitions from post-doctoral fellow to junior faculty at a university medical center. The program has three critical components: the sponsor, the advisory committee, and the research program. The sponsor, Dr. David Baltimore has an exceptional record in developing young careers and in initiating basic research programs with important clinical implications. The advisory committee of Drs. David Baltimore, Sam Lux, Stuart Orkin, and Don Kohn consists of a set of academic leaders in the fields of biomedical research, pediatric hematology/oncology and gene therapy. They are uniquely qualified and committed to advise the PI in both his career development and research program. Finally, the research program is focused on the important field of gene targeting in vertebrate cells. Its overall aim is to understand the genetics of gene targeting (GT) using a green fluorescent protein (GFP) gene targeting system that the PI developed. The specific aims of the research proposal include understanding: 1) the cell cycle regulation of GT; 2) the rate of GT in DT40 cells; 3) the role of Rad52 in inhibiting GT and; 4) the rate of GT in cells with mutations involved in DNA double-stranded break repair. It is hoped that such studies will lead to advances in the field of gene therapy and in the treatment of children with monogenic diseases, such as sickle cell disease.